Studies of socio-economic status (SES) have figured prominently in research related to a variety of health outcomes, although the question remains as to whether SES contributes to the aetiologies of congenital anomalies. This study examines the association of SES with risks of conotruncal heart defects and orofacial clefts, using interview data from 696 case mothers (86% of eligible) and 734 (78%) control mothers from a population-based case-control study. Socio-economic measures from maternal interview included mother's education and employment. Reported addresses were linked with the US census to characterise six measures of neighbourhood SES (education, poverty, unemployment, occupation, crowding and rental occupancy). Results were adjusted for race-ethnicity, multivitamin/mineral supplement intake, cigarette smoking and binge drinking. Results for individual and neighbourhood measures suggested that low SES was associated with increased risk of d-transposition of the great arteries (dTGA), reduced risk of tetralogy of Fallot (TOF), but was not associated with risk of orofacial clefts. For example, when examining odds ratios (OR) that compared risks among women whose neighbourhoods were in the lowest vs. highest quartile of the census-based SES measures, ORs for five of the six measures were> 1.4 for dTGA, and ORs for all six measures were < 0.7 for TOF. ORs for clefts tended to be closer to 1. This study suggests that SES risks are birth defect specific.